BackgroundPolycystic ovary syndrome (PCOS) and obesity can both disrupt reproductive function. However, the extent to which obesity contributes to PCOS manifestations is not very clear. This study aimed to disentangle the relative contributions of PCOS and obesity for reproductive dysfunction in women undergoing in vitro fertilization (IVF).MethodsA total of 129 women undergoing IVF treatments were recruited. Women were allocated into four groups according to body mass index (BMI) and PCOS diagnosis: normal-weight controls (n = 33; 21.70 ± 1.85 kg/m²), overweight/obesity controls (n = 28; 28.35 ± 3.05 kg/m²), normal-weight PCOS (n = 31; 21.92 ± 1.95 kg/m²), and overweight/obesity PCOS (n = 37; 31.67 ± 5.03 kg/m²). Circulating levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), glucose and insulin were measured in all groups, while insulin resistance was assessed by the Homeostatic Model (HOMA-IR). Additionally, on the oocyte retrieval day, ∆4-androstenedione, testosterone, progesterone and sex hormone-binding globulin (SHBG), were measured in plasma and follicular fluid (FF). IVF outcomes evaluated included the number of oocytes retrieved, oocyte immaturity, as well as fertilization and blastocyst formation rates. A multivariate analysis was performed to determine the independent effects of PCOS and obesity for reproductive and metabolic parameters.ResultsWomen with PCOS presented significantly higher AMH levels, LH: FSH ratio, and lower FF progesterone levels, confirming these as PCOS-specific signatures regardless of BMI. In contrast, women with overweight/obesity had lower plasma and FF SHBG levels and greater HOMA-IR, independently of PCOS. Furthermore, ∆4-androstenedione and testosterone levels in plasma and FF were significantly higher in women with PCOS and overweight/obesity as compared to normal-weight women with PCOS. Despite the higher oocyte retrieval rates in women with PCOS, no differences in oocyte immaturity, fertilization and blastocyst formation rates were observed.ConclusionsPCOS and obesity independently disrupt female reproductive function suggesting that features associated with each condition may differ. Furthermore, our study shows that obesity exacerbates hyperandrogenism in women with PCOS, highlighting a synergistic detrimental impact on female reproductive function.

BackgroundInfertility affects a significant portion of the global population, with male factor infertility contributing to nearly half of all cases. The success of assisted reproductive technologies (ART), such as in vitro fertilization (IVF), depends on selecting high-quality sperm with optimal motility, morphology, and DNA integrity. The Q300™ device offers a novel approach for improving sperm selection. Utilizing an advanced optical imaging system, the Q300™ isolates the morphologically compliant sperm cells sperm for injection into the oocytes. This study aims to assess the usability and preliminary clinical outcome of the Q300™ device under “real-life conditions” in a fertility laboratory setting.MethodsPreliminary clinical data collected from Barzilai Medical Center with or without using the technology were compared to the Key Performance Indicators (KPI) for ART laboratories according to the Vienna Consensus.ResultsThe data suggest that the Q300™ significantly improved day-3 embryo development, blastulation, and cumulative pregnancy rates.ConclusionsBy offering a more refined and efficient selection process, the Q300™ has the potential to redefine clinical practice in infertility treatment, providing patients with a higher likelihood of achieving successful outcomes.Trial registrationNCT06232720. Date of registration: 15 February 2023.Enrollment of first subject: 20 August 2023. For more information, visit: https://clinicaltrials.gov/study/NCT06232720.

BackgroundThe incidence of twin pregnancies has risen in recent decades, which is mainly attributable to assisted reproduction technology. Fetal reduction (FR) can significantly reduce the risk of low birthweight (LBW) in twins; however, the LBW risk is higher in singletons reduced from twins than that in primary singletons. Factors including maternal factors and FR timing may affect the LBW risk after FR, but there are no relevant prediction models reported to date. Our main study objective was to develop a nomogram to predict LBW risk in singleton pregnancies reduced from dichorionic (DC) twins.MethodsWe retrospectively reviewed and analysed data from women with DC twin pregnancies who underwent FR at Women's Hospital School of Medicine, Zhejiang University between July 2005 and August 2021. Least absolute shrinkage and selection operator (LASSO) regression was used to identify relevant variables associated with LBW. A nomogram was constructed and receiver operating characteristic curve, calibration curves, and decision clinical analysis were used for model performance assessment and visualization. The model was evaluated using cohorts produced by 500 resampling bootstrap analysis to test its stability.ResultsA total of 471 patients were enrolled in the analysis. Finally, seven independent predictive factors for LBW were identified and integrated to construct the nomogram, including maternal height, nulliparous, conception method, reasons for FR, gestational age at FR, gestational diabetes, and pregnancy hypertensive disease. The area under the receiver operating characteristic curve of our prediction model was 0.793, which was validated in internal confirmation (0.762) using bootstrap analysis. The nomogram had well-fitted calibration curves. Decision curve analysis demonstrated that the nomogram was clinically useful.ConclusionWe first developed a reliable predictive nomogram for the risk of LBW in DC twin pregnancies reduced to singleton pregnancies, providing a useful guide for clinicians and patients in making appropriate decisions regarding FR.

Endocrine disrupting chemicals (EDCs) are ubiquitous in the environment and have been shown to interfere with the endocrine system, leading to adverse effects on reproductive health. In females, EDC exposure has been linked to menstrual irregularities, infertility, and pregnancy complications. Epigenetic regulation, which involves modifications to DNA and histones that do not alter the underlying genetic code, plays a crucial role in female reproduction. EDCs have been shown to disrupt epigenetic mechanisms, leading to changes in gene expression that can have long-term effects on reproductive outcomes. Several EDCs, including bisphenol A (BPA) and phthalates, dioxins, and polychlorinated biphenyls (PCBs), have been shown to alter DNA methylation patterns and histone modifications in female reproductive tissues. These changes can lead to altered expression of genes involved in ovarian function, implantation, and placental development. Here, we integrate epidemiological and experimental evidence from the last 20 years to profile the types of diseases that EDCs trigger in the female reproductive system in relation to the uterus, and the corresponding molecular mechanisms that have been studied. In addition, this review will outline the state of knowledge of EDC epigenetic regulation in the uterus and how it impacts reproductive health, as well as identify areas for future research.

BackgroundThe aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor historically recognized for its role in the regulation of toxicity mediated by environmental chemicals. Recent research points to AhR’s critical participation in male reproductive physiology, particularly in spermatogenesis, hormone signaling, and the maintenance of sperm quality. Both endogenous ligands (e.g., dietary and gut microbiota-derived metabolites) and exogenous pollutants (e.g., dioxins and benzo-α-pyrene) influence AhR-mediated pathways, making it a key link between environmental exposures and male fertility.ResultsThis review highlights AhR’s influence on the male reproductive system, emphasizing the role of endogenous AhR ligands and AhR expression in the maturation and function of male reproductive organs. Environmental AhR agonists have been shown to induce oxidative stress, hormonal imbalance, and sperm DNA damage, which impact harmfully on the spermatogenesis process, which leads to reproductive abnormalities. Conversely, certain natural compounds such as resveratrol, curcumin, and lycopene appear to antagonize AhR activation and reduce its negative effects, thus offering potential protective benefits against male reproductive toxicity. Nevertheless, discrepancies persist regarding the exact interplay between AhR signaling and critical reproductive hormones such as testosterone and LH, and it remains unclear how transgenerational epigenetic changes triggered by AhR activation might affect long-term male fertility.ConclusionAhR is pivotal in male reproductive physiology, influencing spermatogenesis, sperm quality, and hormone regulation through its interactions with both endogenous and environmental ligands. Persistent pollutants such as dioxins and polycyclic aromatic hydrocarbons cause oxidative damage and hormonal disturbances via AhR, contributing to reduced sperm quality and fertility.Graphical The Impact of ligands of Aryl Hydrocarbon Receptor (AhR) on Male Reproductive Health. →, activation; ⊣, inhibition; DEHP, Di(2-ethylhexyl) phthalate; I3C, indole-3-carbinol; PAH, polycyclic aromatic hydrocarbon; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin (Created by Biorender.com).

BackgroundThe synergistic impact of isolate maternal hypothyroxinaemia (IMH) and other modulators on fetal growth outcomes is unknown. This study was aimed to determine whether third trimester IMH [free thyroxine level (FT4) below the the 5th percentile and thyroid stimulating hormone (TSH) between the 5th and 95th percentiles] and prenatal body mass index (BMI) jointly increase the risk of large for gestational age (LGA) deliveries.MethodsA retrospective analysis was conducted on 11,478 Chinese pregnant women with laboratory data (including thyroid hormone levels and routine biochemical tests) and hospitalization records from a specialized hospital.ResultsThe prevalence of obesity (BMI ≥ 30 kg/m2) and IMH was 20.1% (2312/11478) and 4.5% (519/11478), retrospectively. Women with obesity had a 6.96-fold greater risk of IMH (95% CI: 4.58, 10.58) and a 5.88-fold increased risk of LGA (95% CI: 4.87, 7.11) than those with normal weight (BMI < 25 kg/m2), while women with IMH had a 1.32-fold increased risk of LGA (95% CI: 1.05, 1.65) than euthyroid women. The positive associations of LGA risk with obesity and IMH remained robust in sensitivity analyses conducted among women aged < 35 years, primiparas, and those without pregnancy complications. Compared to euthyroid women with normal weight, women with obesity and IMH had a 7.60-fold higher risk of LGA (95% CI: 5.26, 10.97). Additionally, a significant interaction between BMI categories and IMH on LGA was observed (P < 0.013). Subgroup analyses validated this interaction among women with aged < 35 years, multiparity, and non-pregnancy complications.ConclusionsObesity and IMH in late pregnancy are both associated with an increased risk of LGA newborns, and their coexistence may further amplifies this risk; prenatal BMI and thyroid hormone levels could serve as potential indicators for identifying individuals at elevated LGA risk.

BackgroundAccording to data from numerous research studies and reviews, the efficiency of the oocyte slow-freezing method is believed to be compromised. Here, we attempt to challenge this notion by showing our retrospective evaluation of the efficiency of the traditional vs. successfully modified method of slow-frozen oocyte recovery compared with that of vitrified oocytes. Specifically, we compared the efficiency of a modified thawing/rehydration system applied to oocytes that had already been slow-frozen with the effects of oocyte vitrification. Moreover, we verified this comparison using chemical activation of slow-frozen vs. vitrified oocytes and parthenogenetic embryo development.ResultsTwenty-two and 73 thawing cycles of slow-frozen oocytes were performed using traditional and modified rehydration methods, respectively. For comparison, 105 warming cycles of vitrified oocytes were analyzed. The survival rate of oocytes subjected to the traditional rehydration method was 65.1%. In contrast, significantly higher ratios of 89.8% and 89.7% of oocytes survived the thawing/warming procedure performed according to the modified rehydration procedure or vitrification, respectively (P ≤ 0.0001). Clinical pregnancy and implantation rates tended to be higher after a transfer of embryos developed in the modified rehydration group vs. traditional rehydration group (33.8% and 25.5% vs. 23.5% and 13.8%, respectively) and were comparable to vitrification effects (30.1% and 26.6%). Transfer of embryos developed after modified post-thawing rehydration method resulted in 23 births with 25 healthy and one preterm baby, not significantly different from 28 births reported after oocyte vitrification. Slow-frozen oocytes that were chemically activated after the superior modified rehydration method gave similar survival (91.9% vs. 99.0%), activation (76.0% vs. 64.6%) and blastocyst rates (15.2% vs. 9.4%) in comparison with vitrified oocytes, respectively.ConclusionsThe modified post-thawing rehydration method applied to slow-frozen oocytes offers benefits in terms of higher oocyte survival, fertilization, and development or activation rates, comparable to the respective measures of vitrified oocytes and, in clinical settings, high pregnancy, implantation, and birth rates. It may bring new hope to patients who have slow-frozen oocytes stored in IVF clinics.

BackgroundTo evaluate whether there was a difference in outcome between pulsatile gonadotropin releasing hormone (GnRH) therapy and human chorionic gonadotropin/human menopausal gonadotropin (hCG/HMG) therapy for induction of spermatogenesis in post-pubertal male patients with congenital hypogonadotropic hypogonadism (CHH).MethodsThis was a single-center retrospective cohort study conducted at the Andrology Center of a university hospital. A total of 155 postpubertal CHH patients who met the inclusion criteria underwent spermatogenic induction at the same andrology center. All patients used pulsatile GnRH therapy or hCG/HMG therapy for at least 6 months. The effects of spermatogenic induction therapy and testicular growth were evaluated. Logistic regression analysis was used to identify statistically significant factors which could predict the outcome of treatment.ResultsThere was no difference in the efficiency of successfully inducing spermatogenesis between pulsatile GnRH therapy and hCG/HMG therapy (82.1% vs. 75.8%, P: 0.356), nor was there a difference in sperm concentration category (SCC) (P: 0.284). However, the mean time required for pulsatile GnRH therapy was shorter (12.34 vs. 14.74 months, P: 0.038). At the treatment endpoint, total testicular volume (TTV) was greater with pulsatile GnRH therapy compared with hCG/HMG therapy (15 vs. 12 ml, P: 0.010), and there was still no difference in SCC (P: 0.310). Multivariate logistic regression analysis showed that only baseline TTV was statistically significant predictor of induced spermatogenic success (odds ratio, OR: 1.156, 95% confidence interval, CI: 1.013, 1.319). The area under receiver operating characteristic curve was 0.635, a sensitivity of 0.661, and a specificity of 0.588. In addition, multiple linear regression analysis demonstrated that younger age at treatment initiation and higher baseline TTV were significantly associated with increased sperm concentration at the end of treatment.ConclusionPulsatile GnRH therapy was similar to hCG/HMG therapy in inducing spermatogenesis in post-pubertal CHH patients, but it took less time and was more beneficial to testicular development. Larger baseline TTV may mean a better spermatogenic outcome. It was necessary for patients to have more information about spermatogenesis therapy in order to make reasonable medical decisions.Clinical trial registration numberChinese Clinical Trial Registry. ChiCTR2400086876. Retrospectively registered on July 5, 2024.

BackgroundInsulin-like peptide (INSL3), belonging to the insulin-like peptide family, is produced by theca interna cells within antral follicles and the corpora lutea. It is hypothesized that INSL3 is integral to the initial development and function of antral follicles, specifically through its regulatory effect on androgen biosynthesis in the thecal cells of these follicles. Moreover, INSL3 is implicated in the modulation of the ovarian microenvironment, which is essential for facilitating the maturation of oocytes. Our study investigates if circulating and follicular fluid INSL3 levels serve as biomarkers for ovarian reserve and IVF success in women with unexplained infertility (UI) and diminished ovarian reserve (DOR).MethodsThis prospective study included 75 women (25 with DOR, 24 with UI) undergoing IVF and 26 controls with normal ovarian reserve. Serum and follicular fluid INSL3 levels were measured, and their association with ovarian reserve markers, pregnancy rates, and live birth rates (LBR) was analyzed.ResultsCirculating (p = 0.001) and follicular fluid (p < 0.001) INSL3 levels, AMH levels (p < 0.001) and AFC (p < 0.001) were significantly lower and basal E2 level (p < 0.001) were significantly higher in DOR group compared to the UI and control groups. Circulating INSL3 positively correlated with serum anti-Müllerian hormone (AMH) and antral follicle count (AFC), and negatively correlated with follicle-stimulating hormone (FSH). Positive pregnancy rates and LBR were significantly lower in the DOR group. Basal FSH was identified as a significant predictor of LBR.ConclusionsThe current study presents that although the serum and follicular fluid INSL3 levels are significantly lower in women with DOR, the narrow margin between the DOR and control groups indicates that INSL3measurement may be insufficient on its own to be of diagnostic value for DOR. Further research with larger sample sizes is needed to validate these findings and explore the role of INSL3 in ovarian aging and infertility treatment.

BackgroundMost methods of ovarian stimulation rely on gonadotropin modulation. However, abnormal anti-Müllerian hormone concentrations are frequent in infertility, suggesting that defects in the gonadotropin-independent period of folliculogenesis preceding cyclic recruitment (i.e., basal follicular growth) may often occur. We need to better understand basal follicular growth and determine how to improve it.MethodsSection I summarizes a literature search concerning preantral and early antral folliculogenesis, cyclic recruitment, and selection. Section II presents current knowledge about interventions involving early antral folliculogenesis and cyclic recruitment.ResultsWhile folliculogenesis following cyclic recruitment is gonadotropin-dependent, basal follicular growth is not. Basal follicular growth is regulated by follicle-stimulating hormone and local communication between the oocyte and its granulosa and thecal cells involving gap junctions and many autocrine/paracrine factors. This local communication sustains growth synergistically with follicle-stimulating hormone, but also suppresses this hormone to induce granulosa cell differentiation. As a follicle develops, its responsiveness to gonadotropin progressively increases. Section II describes 4 interventions affecting early antral folliculogenesis, including granulocyte colony-stimulating factor priming, bromocriptine rebound, carbohydrate metabolism intervention, and danazol priming, which have improved embryo development and live birth rate in patients with previous failures.ConclusionBasal follicular growth modulation can increase live birth rates.